ROBO3: Roundabout Guidance Receptor 3
Axon guidance receptor critical for hindbrain and spinal cord development; mutations cause horizontal gaze palsy with progressive scoliosis (HGPPS).
Gene Information Card
| Symbol | ROBO3 |
|---|---|
| Full Name | Roundabout Guidance Receptor 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 11q24.2 |
| NCBI Gene ID | 64221 ncbi.nlm.nih.gov/gene/64221 |
| Ensembl ID | ENSG00000154134 |
| UniProt ID | Q96MS0 |
| OMIM ID | 608630 |
| HGNC ID | 13433 |
| Aliases | RBIG1, RIG-1, roundabout homolog 3 |
Description
ROBO3 encodes a transmembrane receptor of the roundabout (Robo) family that mediates axon guidance and cell migration. It is essential for the proper crossing of spinal cord commissural axons and for the development of hindbrain motor nuclei. Loss-of-function mutations cause horizontal gaze palsy with progressive scoliosis (HGPPS), a disorder characterized by congenital horizontal eye movement restriction and progressive spinal curvature.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Horizontal gaze palsy with progressive scoliosis (HGPPS) | Biallelic loss-of-function mutations disrupt ROBO3-mediated axon guidance, preventing normal decussation of corticospinal tracts and trochlear nerve development. | ClinVar, OMIM |
| Congenital fibrosis of extraocular muscles (CFEOM) | Rare missense variants may impair ROBO3 signaling in oculomotor neuron guidance. | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 10.2 | Medium |
| Spinal cord | 8.5 | Medium |
| Cerebellum | 6.1 | Low |
| Testis | 4.3 | Low |
| Heart | 1.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 12.5 | Neuronal model |
| U-87 MG (glioblastoma) | 9.8 | Glial model |
| HEK293 (embryonic kidney) | 0.5 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1325G>A (p.Arg442Gln) | Missense | Rare | Loss of axon guidance function |
| c.1966C>T (p.Arg656*) | Nonsense | Rare | Premature truncation, loss of function |
| c.2410_2411del (p.Leu804Valfs*12) | Frameshift | Rare | Loss of function |
Mutation functional classification
Loss of Function (LOF)
Most HGPPS-associated mutations are biallelic loss-of-function (nonsense, frameshift, splice-site) leading to absent or non-functional ROBO3 protein.
Gain of Function (GOF)
Not reported for ROBO3.
Dominant Negative (DN)
Not reported; HGPPS is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Axon guidance (KEGG: hsa04360)
• Netrin-1 signaling (Reactome: R-HSA-373752)
• Slit/Robo signaling (Reactome: R-HSA-9013408)
Protein Summary
ROBO3 is a 1,307-amino-acid transmembrane protein with five immunoglobulin-like domains and three fibronectin type III repeats in the extracellular region, and a conserved cytoplasmic domain. It acts as a receptor for Slit ligands, but unlike other Robo family members, ROBO3 can also mediate attractive responses to Netrin-1. It is critical for midline crossing of commissural axons in the spinal cord and for proper decussation of the corticospinal tract.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ROBO3 Knockout HEK293 Cell Line | EDJ-KQ1345 | Human | 64221 | Details Get a Quote |
| ROBO3 Knockout A-549 Cell Line | EDJ-KQ22108 | Human | 64221 | Details Get a Quote |
| ROBO3 Knockout HCT 116 Cell Line | EDJ-KQ22109 | Human | 64221 | Details Get a Quote |
| ROBO3 Knockout HeLa Cell Line | EDJ-KQ22110 | Human | 64221 | Details Get a Quote |
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